PROJECT SUMMARY/ABSTRACT Pediatric opioid use is a public health crisis. In children, prescription opioids are the primary source of non- medical abuse as well as opioid-associated hospitalizations and deaths. Early opioid use in childhood is a known ?gateway? to adulthood dependence and substance abuse disorders. Despite years of research, opioids remain the most commonly prescribed pain medication for children with cancer. These children experience pain from the time of diagnosis into adulthood as survivors, primarily from the treatment for their cancer. The majority of pediatric cancer patients have persistent opioid use in the months following major surgery to cure or to treat their disease. More concerning, studies in childhood cancer survivors show that major surgery increases risk of new-onset and chronic opioid use. The high costs and lack of scalability of traditional distraction-based medical devices for managing pain, such as virtual reality headsets, limit their clinical impact and commercial potential. As cancer patients are often immunocompromised, risk from infectious disease transmission from sharing devices is an additional, possibly life-threatening, concern. Mobile augmented reality applications eliminate these limitations, representing a cost-effective, safe and commercially viable adjunctive tool for pain management in critically ill children. Our goal is to reduce long-term opioid use in children with cancer undergoing major surgery by distracting them from their pain with a scavenger hunt-style mobile AR game while they are recovering in the hospital. To achieve this goal, we have collaborated with pediatric oncologists, anesthesiologists and pain specialists at the MD Anderson Cancer Center and the Baylor College of Medicine (Texas Children?s Hospital). In Phase I, we will demonstrate the feasibility of investigating the ARISE (Augmented Reality Incorporating Spatial Enhancement) game for reducing opioid consumption in the inpatient postoperative wards. In Phase II, we will evaluate the efficacy of the game to reduce immediate and long-term postoperative opioid use in children with cancer undergoing major treatment-related surgery in a multi-site randomized controlled clinical trial (AURORA trial: Augmented Reality for Opioid Reduction in Childhood Cancer). To our knowledge, this is the first RCT to investigate mobile augmented reality for opioid reduction in pediatric cancer patients or for postoperative opioid reduction in any pediatric population. As the majority of children with cancer are expected to survive long-term, the benefits of reducing and preventing chronic opioid use in this high-risk, refractory pain population will last over the lifetime of a child.